The complexation of diols and boronic acid in aqueous solution results in reversible covalent bonding through the formation of a boronate ester linkage, and this reaction has been extensively used in biomedical application as an efficient method of detecting sugar under specific conditions (see Asher et al. J. Am. Chem. Soc. 2003, 125, 3322-3329; Dowlut, et al. J. Am. Chem. Soc. 2006, 128, 4226; Winblade et al. J. Biomedical Materials Research 2001, 59, 618). The complexation reaction occurs at solution pH which is higher than the pKa of the two reagents used (see Yan et al. Tetrahedron 2004, 60, 11205-11209; Springsteen et al. Tetrahedron 2002, 58, 5291). Because the pKa of phenyl boronic acid is very high (˜8.8), this complexation reaction has not been generally reported to occur under physiological conditions.
Hydrogels are made from three-dimensional polymeric networks, which are hydrophilic and cross-linked via covalent or non-covalent interactions. Because they are homogenous soft materials with physical properties similar to those of soft tissues, there is great interest in using hydrogels for a number of biomedical applications, including in sensors, in separation systems, and in various biomaterials. Recently, efforts have focused on stimuli-responsive hydrogels, which have the ability to respond to external triggers like pH, temperature, and light. This ability to respond to conditions in the surrounding environment makes such hydrogels suitable for a range of applications in medicine and tissue engineering.
Research on stimuli-responsive hydrogels has specifically focused on physical (non-covalently bonded) hydrogels. However, physical hydrogels are generally less stable and have poorer mechanical properties than covalently cross-linked hydrogels. Therefore, there is a need in the art for hydrogels that integrate into a single material the stimuli-responsiveness of certain physical gels with the stability provided by chemical (covalently bonded) hydrogels. Ideally, such hydrogels would be self-healing and would form under physiological conditions.